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Second day highlights from the International Menopause Society conference 2014

6 May 2014



Mirena provides many benefits
The progestogen releasing intrauterine system, Mirena has now been in use since 1990 and continues to be very successful for reducing heavy menstrual bleeding in women both premenopausally and in those in the perimenopause. With increasing age, periods often increase both in heaviness and irregularity. Evidence presented confirmed that following insertion of Mirena, while there is often an initial increase in the number of days of bleeding, particularly spotting, this returns to baseline by two months in most women and then gradually decreases thereafter. Follow up studies have shown that Mirena is more effective than the standard treatments of Tranexamic acid, Mefenamic acid, combined hormonal contraceptives and oral progestogens in reducing heavy menstrual bleeding, with 83% of women becoming bleed-free after 12 months of use of Mirena in the perimenopause. For Health Related Quality of Life, Mirena is as good as the use of endometrial ablation or hysterectomy, as well as being cost effective.
Whether Mirena is used for contraception during the premenopause or contraception and control of bleeding during the perimenopause, good bleeding control persists, which is not worsened by adding in estrogen replacement for control of menopausal symptoms. Use of Mirena for the progestogenic protection of the womb lining (endometrium) while taking estrogen HRT, provides an excellent combination of continuing contraception, bleeding control and endometrial protection while estrogen controls menopausal symptoms. Adverse effects of Mirena and estrogen are reported as insignificant with no detrimental effects on cardiovascular risk factors and no conclusive evidence of any increased breast cancer risk from a large case control study.

Life after breast cancer can be difficult
Women can experience many symptoms and have to cope with many distressing issues after a diagnosis of breast cancer such as fatigue, anxiety, fertility issues, fear of recurrence, side effects of treatment, relationship issues, and hormonal effects. How best to help and what support and treatments are available continues to be challenging and often lacking in clear evidence base.
For menopausal symptoms, whether the menopause occurs naturally or as a result of treatment for breast cancer, diet and lifestyle issues should be discussed first since reducing weight and reducing alcohol if applicable may help menopausal symptoms but can also reduce risk of breast cancer recurrence. Specific prescribed non-hormonal treatments can be considered for symptoms such as flushes and sweats and moisturisers and lubricants can be used for menopausal vaginal dryness. Low dose antidepressants have been shown to reduce flushes and sweats, but care must be taken in the choice of type since some can reduce the effect of Tamoxifen. For some women, vaginal estrogen and even HRT can be considered when simple measures do not control symptoms, after full discussion. Psychological support may be required and consideration should be given to optimising later heart and bone health due to possible effect from early menopause and effect of certain breast cancer treatments. No new data was presented but the discussion raised awareness of the challenges faced.

Call for more detail in assessing ovarian cysts
Many postmenopausal women are referred to gynaecology clinics because of the finding of an ovarian cyst on a scan, which may have been arranged for a non-related reason. While it is known that ovarian cancer affects 1.4% of women, most postmenopausal women with cysts measuring less than 5cm are unlikely to have cancer, especially if the cyst is described as simple. Measurement of blood level of CA125 is not always helpful but a new tumour marker is under investigation. Meanwhile, it is felt that more detailed examination of the cyst by scan would help in determining which women should be offered surgery, and who can be advised to avoid unnecessary intervention.

Could Metformin be helpful for overweight menopausal women?
Menopause is known to be associated with increases in body fat, Body Mass Index (BMI), resistance to insulin, glucose intolerance and risk of developing Type 2 Diabetes. Metformin has been used for many years to treat Type 2 diabetes and acts by increasing sensitivity to insulin. A trial comparing the use of Metformin and placebo in women aged 35 to 65 who were obese with a BMI greater than 30 showed a significant decrease in insulin resistance, weight and BMI in the women taking metformin. Limitations are the small study size and further research is indicated.

HRT doses getting lower, does low dose still work?
Over recent years, doses of estrogen used in HRT have gradually reduced, yet still with apparent good effect. Data was presented on the effect on menopausal symptoms of a preparation containing only 0.5mg estradiol along with progestogen. Results showed a rapid reduction in symptoms of flushes and sweats by week 3 of treatment, with a further later improvement which continued. The reduction in symptoms was statistically significantly greater in women taking the ultra low dose HRT compared to those taking placebo. The treatment had excellent tolerability with little or neutral effect on breast density. In treating any condition, there should be no need to take any higher dose of treatment than necessary and this presentation should encourage the use of at least starting with ultra low dose HRT.

Vaginal atrophy - Need for a name change?
It is well known that estrogen deficiency of the menopause often causes significant effects on the vagina (vaginal atrophy) and bladder, leading to vaginal dryness, discomfort during sex and consequent detrimental effects on sexual interest, response, sexual function, relationships and quality of life, as well as bladder problems yet symptoms are hugely under reported and under treated. Reasons for under reporting include embarrassment, assumptions that nothing can be done, acceptance of condition, and social taboos. A recent survey showed that 70% of women with vaginal atrophy had not discussed their problem with a healthcare professional, (previous survey on Menopause Matters showed that around 80% had not discussed their symptoms). Effective, safe treatments are available in various forms of low dose vaginal estrogen, but it is essential that women are able to report and discuss their symptoms, and that healthcare professionals routinely engage in open and sensitive discussion with postmenopausal women about their urogenital health to ensure that symptomatic atrophy is detected early and appropriately managed. International Menopause Society recommendations state that vaginal estrogen should be commenced early before irrevocable changes occur, that treatment should be continued long term, and that all preparations are effective and patient preference will determine treatment used, yet still treatment levels are low, related to under reporting.
Since it is recognised that women seem to find it difficult to use the word “Vagina” and do not like the term atrophy, along with recognition that the urinary tract can also be affected by estrogen deficiency, a proposal has been made to use the term Genitourinary Syndrome of Menopause (GSM). Anything that will help to make it easier for women to report symptoms and consider treatment, and for healthcare professionals to “open the door” to discuss the possibility of symptoms by asking appropriate questions is welcomed and it will be interesting to see if this will make a difference.

Is HRT good for the brain?
The effect of estrogen lack on various aspects of brain function and the effect of replacing estrogen has long been debated. New data from the KEEPS cognitive study were presented and showed that the use of HRT started within a few years of the menopause provided no effect, good or bad, on aspects such as verbal learning and memory, auditory attention, working memory, visual attention or tests of cognition compared to women taking placebo. Regarding mood, a beneficial effect of estrogen only therapy was seen on mood, and the beneficial effect was sustained over 4 years, along with beneficial effect on depression and tension and anxiety. No difference between women taking HRT and those not taking HRT was seen for vigour, fatigue, confusion, or bewilderment. A trend for benefit for estrogen only therapy was seen for memory function tests, though this was not statistically significant. While it is reassuring that no adverse effect was shown for use of HRT, these results would indicate that HRT should not be relied upon for improving these aspects of brain function.

Are Phytoestrogens good for the brain?
Previous trials have given varying results.
WISH trial - Women’s Isoflavone soy Health trial, was a recent randomised controlled trial where women were randomised to taking 25mg isoflavone-rich soy protein daily or 25ml milk protein. Results showed no change in global cognition but a possible improvement in visual memory, though it is not clear how clinically meaningful this was.

TSEC, a new approach in menopausal therapy
After widespread publicity around results from WHI trial, suggesting increased risks from use of HRT, reanalysis of data has gradually led to the belief that risks of replacing estrogen for control of estrogen deficiency symptoms, and for later consequences of estrogen deficiency is safe, with minimal risks. The addition of progestogen to protect the womb lining from estrogenic stimulation adds some risk, albeit very small, is influenced by the type of progestogen and still provides more benefits than risks for most women when used appropriately.
TSEC (Tissue Selective Estrogen Complex) is a new therapy area, which combines estrogen with a Selective Estrogen Receptor Modulator (SERM). One such product has recently become licensed and is likely to be available in the UK later this year. The combination of conjugated equine estrogen with bazedoxifene provides the benefits of estrogen without the need for progestogen, since the bazedoxifene targets estrogen receptors in the womb and breast, preventing any estrogenic stimulation of these tissues. Data presented demonstrated good effect on controlling menopausal symptoms, no stimulation of womb lining with therefore no bleeding problems, favourable bone effect and apparent lack of effect on breast cancer risk, though data was only presented for 2 years use. Any new option is welcomed and further information on longer term data is awaited.

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